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Anatomy and Cell Biology
Anatomy and Cell Biology 4429A
Paul Walton

Statin works inhibit endogenous level of LDL synthesis Statin drugs inhibit HMGCoA reductase which is the first step in the synthesis of cholesterol Xanthomahigh cholesterol ends up being put in walls of tendons LDL receptor is the primary causeat least 100 different mutations in this gene Roughly speaking if you have this disease you must lower this cholesterol Albumin binds fat and can transport it in the blood HMGCoA can be inhibited by purified LDL which ends up with a biochemical negative feedback pathway If I treat cells from patients with Familial Hypercholesteria it doesnt work This signifies that this negative feedback control regulated by increased concentration of LDL does not work and is lost These patients however did not have a defect in HMGCoA as one would think first I take LDL particles and determine how many of them have been taken up by radiolabelling them This experiment showed that the binding was saturable In FH cells there is very little binding and very little uptake Thus these cells are not binding LDL Another role for Hsp70turns the coated vesicle into an uncoated vesicle The LDL receptor has a portion inside the membrane of the cell which helps internalize the cargo with the help of an adaptor protein that the outside portion has bound to A mutation in this region of the LDL receptor still allows binding the receptor in the ECM however does not allow internalization of this cargo This would cause saturation of t
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